The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF str...The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.展开更多
Lithium-ion batteries(LiBs)with high energy density have gained significant popularity in smart grids and portable electronics.LiMn_(1-x)Fe_(x)PO_(4)(LMFP)is considered a leading candidate for the cathode,with the pot...Lithium-ion batteries(LiBs)with high energy density have gained significant popularity in smart grids and portable electronics.LiMn_(1-x)Fe_(x)PO_(4)(LMFP)is considered a leading candidate for the cathode,with the potential to combine the low cost of Li Fe PO_(4)(LFP)with the high theoretical energy density of LiMnPO_(4)(LMP).However,quantitative investigation of the intricate coupling between the Fe/Mn ratio and the resulting energy density is challenging due to the parametric complexity.It is crucial to develop a universal approach for the rapid construction of multi-parameter mapping.In this work,we propose an active learning-guided high-throughput workflow for quantitatively predicting the Fe/Mn ratio and the energy density mapping of LMFP.An optimal composition(LiMn_(0.66)Fe_(0.34)PO_(4))was effectively screened from 81 cathode materials via only 5 samples.Model-guided electrochemical analysis revealed a nonlinear relationship between the Fe/Mn ratio and electrochemical properties,including ion mobility and impedance,elucidating the quantitative chemical composition-energy density map of LMFP.The results demonstrated the efficacy of the method in high-throughput screening of LiBs cathode materials.展开更多
The capture of CO_(2)from CO_(2)/H_(2)gas mixtures in syngas is a crucial issue for hydrogen production from steam methane reforming in industry,as the presence of CO_(2)directly affects the purity of H_(2).A combinat...The capture of CO_(2)from CO_(2)/H_(2)gas mixtures in syngas is a crucial issue for hydrogen production from steam methane reforming in industry,as the presence of CO_(2)directly affects the purity of H_(2).A combination of a high-throughput screening method and grand canonical Monte Carlo simulation was utilized to evaluate and screen 1725 metal–organic frameworks(MOFs)in detail as a means of determining their adsorption performance for CO_(2)/H_(2)gas mixtures.The adsorption and separation performance of double-linker MOFs was comprehensively evaluated using eight evaluation indicators,namely,the largest cavity diameter,accessible surface area,pore occupied accessible volume,porosity,adsorption selectivity,working capacity,adsorbent performance score and percent regeneration.Six optimal performance frameworks were screened to further study their single-component adsorption and binary competitive adsorption of CO_(2)/H_(2)respectively.The CO_(2)adsorption selectivity at different CO_(2)/H_(2)feed ratios was also evaluated,which indicated their excellent adsorption and separation performance.The microscopic adsorption mechanisms for CO_(2)and H_(2)at the molecular level were investigated by analyzing the radial distribution function and density distribution.This study may provide directional guidance and reference for subsequent experiments on the adsorption and separation of CO_(2)/H_(2).展开更多
For the advancement of fast-charging sodium-ion batteries(SIBs),the synthesis of cutting-edge cathode materials with superior structural stability and enhanced Na+diffusion kinetics is imperative.Multiphase layered tr...For the advancement of fast-charging sodium-ion batteries(SIBs),the synthesis of cutting-edge cathode materials with superior structural stability and enhanced Na+diffusion kinetics is imperative.Multiphase layered transition metal oxides(LTMOs),which leverage the synergistic properties of two distinct monophasic LTMOs,have garnered significant attention;however,their efficacy under fast-charging conditions remains underexplored.In this study,we developed a high-throughput computational screening framework to identify optimal dopants that maximize the electrochemical performance of LTMOs.Specifically,we evaluated the efficacy of 32 dopants based on P2/O3-type Mn/Fe-based Na_(x)Mn_(0.5)Fe_(0.5)O_(2)(NMFO)cathode material.Multiphase LTMOs satisfying criteria for thermodynamic and structural stability,minimized phase transitions,and enhanced Na^(+)diffusion were systematically screened for their suitability in fast-charging applications.The analysis identified two dopants,Ti and Zr,which met all predefined screening criteria.Furthermore,we ranked and scored dopants based on their alignment with these criteria,establishing a comprehensive dopant performance database.These findings provide a robust foundation for experimental exploration and offer detailed guidelines for tailoring dopants to optimize fast-charging SIBs.展开更多
Barrett's esophagus(BE) is a change in the esophageal lining and is known to be the major precursor lesion for most cases of esophageal adenocarcinoma(EAC).Despite an understanding of its association with BE for m...Barrett's esophagus(BE) is a change in the esophageal lining and is known to be the major precursor lesion for most cases of esophageal adenocarcinoma(EAC).Despite an understanding of its association with BE for many years and the falling incidence rates of squamous cell carcinoma of the esophagus, the incidence for EAC continues to rise exponentially. In association with this rising incidence, if the delay in diagnosis of EAC occurs after the onset of symptoms,then the mortality at 5 years is greater than 80%. Appropriate diagnosis and surveillance strategies are therefore vital for BE. Multiple novel optical technologies and other advanced approaches are being utilized to assist in making screening and surveillance more cost effective. We review the current guidelines and evolving techniques that are currently being evaluated.展开更多
Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinicallyavailable diagnostic methods are mainly based on the use of either X-...Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinicallyavailable diagnostic methods are mainly based on the use of either X-rays or ultrasound(US). All X-ray based methods provide a measure of bone mineral density(BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry(DXA) is considered the current 'gold standard' for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations(e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound(QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this 'silent disease' and show up recent advances for its prevention and improved management through early diagnosis.展开更多
Finding energetic materials with tailored properties is always a significant challenge due to low research efficiency in trial and error.Herein,a methodology combining domain knowledge,a machine learning algorithm,and...Finding energetic materials with tailored properties is always a significant challenge due to low research efficiency in trial and error.Herein,a methodology combining domain knowledge,a machine learning algorithm,and experiments is presented for accelerating the discovery of novel energetic materials.A high-throughput virtual screening(HTVS)system integrating on-demand molecular generation and machine learning models covering the prediction of molecular properties and crystal packing mode scoring is established.With the proposed HTVS system,candidate molecules with promising properties and a desirable crystal packing mode are rapidly targeted from the generated molecular space containing 25112 molecules.Furthermore,a study of the crystal structure and properties shows that the good comprehensive performances of the target molecule are in agreement with the predicted results,thus verifying the effectiveness of the proposed methodology.This work demonstrates a new research paradigm for discovering novel energetic materials and can be extended to other organic materials without manifest obstacles.展开更多
Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of m...Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.展开更多
Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult hom...Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.展开更多
Objective To develop a high-throughput screening assay for Farnesoid X receptor （FXR） agonists based on mammalian one-hybrid system （a chimera receptor gene system） for the purpose of identifying new lead compound...Objective To develop a high-throughput screening assay for Farnesoid X receptor （FXR） agonists based on mammalian one-hybrid system （a chimera receptor gene system） for the purpose of identifying new lead compounds for dyslipidaemia drug from the chemical library. Methods cDNA encoding the human FXR ligand binding domain （LBD） was amplified by RT-PCR from a human liver total mRNA and fused to the DNA binding domain （DBD） of yeast GAL4 of pBIND to construct a GAL4-FXR （LBD） chimera expression plasmid. Five copies of the GAL4 DNA binding site were synthesized and inserted into upstream of the SV40 promoter of pGL3-promoter vector to construct a reporter plasmid pG5-SV40 Luc. The assay was developed by transient co-transfection with pG5-SV40 Luc reporter plasmid and pBIND-FXR-LBD （189-472） chimera expression plasmid. Results After optimization, CDCA, a FXR natural agonist, could induce expression of the luciferase gene in a dose-dependent manner, and had a signal/noise ratio of 10 and Z＇ factor value of 0.65, Conclusion A stable and sensitive cell-based high-throughput screening model can be used in high-throughput screening for FXR agonists from the synthetic and natural compound library.展开更多
Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite thei...Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite their relevance in diseases and the variety of physiological functions they are involved in, ion channels still remain underexploited as drug targets. This, to a large extent, is attributed to the absence of screening technologies that ensure both the quality and the throughput of data. However, an increasing number of assays and technologies have evolved rapidly in the past decades. In this review, we summarized the currently available high-throughput screening technologies in ion channel drug discovery.展开更多
Efficient parallel screening of combinatorial libraries is one of the most challenging aspects of the high- throughput （HT） heterogeneous catalysis workflow. Today, a number of methods have been used in HT catalyst ...Efficient parallel screening of combinatorial libraries is one of the most challenging aspects of the high- throughput （HT） heterogeneous catalysis workflow. Today, a number of methods have been used in HT catalyst studies, including various optical, mass-spectrometry, and gas- chromatography techniques. Of these, rapid-scanning Fourier-transform infrared （FTIR） imaging is one of the fastest and most versatile screening techniques. Here, the new design of the 16-channel HT reactor is presented and test results for its accuracy and reproducibility are shown. The performance of the system was evaluated through the oxidation of CO over commercial Pd/AI203 and cobalt oxide nanoparticles synthesized with different reducer-reductant molar ratios, surfactant types, metal and surfactant concentrations, synthesis temperatures, and ramp rates.展开更多
The globally increasing concentrations of greenhouse gases in atmosphere after combustion of coal-or petroleum-based fuels give rise to tremendous interest in searching for porous materials to efficiently capture carb...The globally increasing concentrations of greenhouse gases in atmosphere after combustion of coal-or petroleum-based fuels give rise to tremendous interest in searching for porous materials to efficiently capture carbon dioxide(CO_2) and store methane(CH4), where the latter is a kind of clean energy source with abundant reserves and lower CO_2 emission. Hundreds of thousands of porous materials can be enrolled on the candidate list, but how to quickly identify the really promising ones, or even evolve materials(namely, rational design high-performing candidates) based on the large database of present porous materials? In this context, high-throughput computational techniques, which have emerged in the past few years as powerful tools, make the targets of fast evaluation of adsorbents and evolving materials for CO_2 capture and CH_4 storage feasible. This review provides an overview of the recent computational efforts on such related topics and discusses the further development in this field.展开更多
Abstract： A simple optimized microplate-based method to assay endo-1,4-β-mannosidase activity was described as an improved high-throughput screening method. A series of experimental conditions were optimized. It is ...Abstract： A simple optimized microplate-based method to assay endo-1,4-β-mannosidase activity was described as an improved high-throughput screening method. A series of experimental conditions were optimized. It is revealed that the optimum measurement procedure is as follows： adding 50μL of diluted enzyme sample and 50 μL substrate, incubating at 45 ℃ for exactly 5 min in micro-plate, mixing with 100 μL 3,5-dinitrosalicylic acid （DNS） reagent, maintaining at boiling point for 15 rain, cooling down to room temperature before determining the ABS value at 540 nm using an ELISA micro-plate reader. The reaction volume of the optimized microplate-assay is reduced to 200μL from 2 500 μL used in the standard β-mannanase macro-assay. The optimized micro-assay is significantly more sensitive in all of the 643 candidates during endo-1,4-β-mannosidase screening. Statistical analyses show that the sensitivity of the optimized micro-method is significantly greater than that of the macro-assay. The optimized method is convenient, fast, and cheap for high throughput enzyme screening.展开更多
To identify the desired hypertherrnophilic variants within a mutant esterase library for the resolution of （R, S）-2- octanol acetate, a simple, reliable, and versatile method was developed in this study. We built a ...To identify the desired hypertherrnophilic variants within a mutant esterase library for the resolution of （R, S）-2- octanol acetate, a simple, reliable, and versatile method was developed in this study. We built a screening strategy including two steps, first we selected agar plate with substrate to screen the enzymatic activity; secondly we used a pH indicator to screen the enantioselectivity. This method could rapidly detect favorable mutants with high activity and enantioselectivity. A total of 96. 2% of tedious screening work can be precluded using this screening strategy. It is an effective screening for alkyl ester and can be applied to relative screening researches. The four improved mutants were screened from the mutant esterase library. Their enantioselectivities, activities, and structures were investigated at different temperatures.展开更多
To develop a new high-throughput screening model for human high-density lipoprotein （HDL） receptor （CD36 and LIMPⅡ analogous-1, CLA-1） agonists using CLA-1-expressing insect cells. Methods With the total RNA of h...To develop a new high-throughput screening model for human high-density lipoprotein （HDL） receptor （CD36 and LIMPⅡ analogous-1, CLA-1） agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA （cDNA） of CLA-1 was amplified by reverse transcription-polymerase chain reaction （RT-PCR）. Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus （AcNPV） into donor vector pFastBacl and recombinant pFastBacl-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacrnid DNA. Recombinant bacrnid-CLA-1 was transfected into Spodopterafrugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA- 1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.展开更多
Thermoelectric materials have drawn extensive interest due to the direct conversion between electricity and heat,however,it is usually a time-consuming process for applying traditional“sequential”meth-ods to grow ma...Thermoelectric materials have drawn extensive interest due to the direct conversion between electricity and heat,however,it is usually a time-consuming process for applying traditional“sequential”meth-ods to grow materials and investigate their properties,especially for thermoelectric films that typically require fine microstructure control.High-throughput experimental approaches can effectively accelerate materials development,but the methods for high-throughput screening of the microstructures require further study.In this work,a combinatorial high-throughput optimization solution of material properties is proposed for the parallel screening and optimizing of composition and microstructure,which involves two distinctive types of high-throughput fabrication approaches for thin films,along with a new portable multiple discrete masks based high-throughput preparation platform.Thus,Bi_(2)Te_(3-x)Se_(x)thin film library with 196 throughputs for locating the optimized composition is obtained in one growth cycle.In addition,another thin film library composed of 31 materials with traceable process parameters is built to further investigate the relationship between microstructure,process,and thermoelectric performance.Through high-throughput screening,the Bi_(2)Te_(2.9)Se_(0.1)film with(00l)orientation is prepared with a peak zT value of 1.303 at 353 K along with a high average zT value of 1.047 in the interval from 313 to 523 K.This method can be also extended to the discovery of other functional thin films with a rapid combinatorial screening of the composition and structure to accelerate material optimization.展开更多
Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China h...Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul virus.No approved antiviral drugs are available for these hantaviral diseases.Here,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources.We identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases.Overall,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS therapy.These findings may offer a starting point for the treatment of patients infected with hantaviruses.展开更多
Zika virus(ZIKV) is associated with severe birth defects and Guillain-Barre′ syndrome and no approved vaccines or specific therapies to combat ZIKV infection are currently available. To accelerate anti-ZIKV therapeut...Zika virus(ZIKV) is associated with severe birth defects and Guillain-Barre′ syndrome and no approved vaccines or specific therapies to combat ZIKV infection are currently available. To accelerate anti-ZIKV therapeutics research, we developed a stable ZIKV GFP-reporter virus system with considerably improved GFP visibility and stability. In this system a BHK-21 cell line expressing DC-SIGNR was established to facilitate the proliferation of GFP-reporter ZIKV. Using this reporter virus system, we established a high-throughput screening assay and screened a selected plant-sourced compounds library for their ability to block ZIKV infection. More than 31 out of 974 tested compounds effectively decreased ZIKV reporter infection. Four selected compounds, homoharringtonine(HHT), bruceine D(BD), dihydroartemisinin(DHA) and digitonin(DGT), were further validated to inhibit wild-type ZIKV infection in cells of BHK-21 and human cell line A549.The FDA-approved chronic myeloid leukemia treatment drug HHT and BD were identified as broad-spectrum flavivirus inhibitors. DHA, another FDA-approved antimalarial drug effectively inhibited ZIKV infection in BHK-21 cells. HHT, BD and DHA inhibited ZIKV infection at a post-entry stage. Digitonin was found to have inhibitory activity in the early stage of viral infection. Our research provides an efficient high-throughput screening assay for ZIKV inhibitors. The active compounds identified in this study represent potential therapies for the treatment of ZIKV infection.展开更多
基金financial support from the National Key Research and Development Program of China(2021YFB 3501501)the National Natural Science Foundation of China(No.22225803,22038001,22108007 and 22278011)+1 种基金Beijing Natural Science Foundation(No.Z230023)Beijing Science and Technology Commission(No.Z211100004321001).
文摘The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.
基金supported by the National Key Research and Development Program of China(No.2021YFB3702102)support from the“Initiation Program for New Teachers”(No.AF0500207)+1 种基金Shanghai Jiao Tong Universitysupport from the Changsha Science and Technology Plan International and Regional Cooperation Project(No.kh2304002)。
文摘Lithium-ion batteries(LiBs)with high energy density have gained significant popularity in smart grids and portable electronics.LiMn_(1-x)Fe_(x)PO_(4)(LMFP)is considered a leading candidate for the cathode,with the potential to combine the low cost of Li Fe PO_(4)(LFP)with the high theoretical energy density of LiMnPO_(4)(LMP).However,quantitative investigation of the intricate coupling between the Fe/Mn ratio and the resulting energy density is challenging due to the parametric complexity.It is crucial to develop a universal approach for the rapid construction of multi-parameter mapping.In this work,we propose an active learning-guided high-throughput workflow for quantitatively predicting the Fe/Mn ratio and the energy density mapping of LMFP.An optimal composition(LiMn_(0.66)Fe_(0.34)PO_(4))was effectively screened from 81 cathode materials via only 5 samples.Model-guided electrochemical analysis revealed a nonlinear relationship between the Fe/Mn ratio and electrochemical properties,including ion mobility and impedance,elucidating the quantitative chemical composition-energy density map of LMFP.The results demonstrated the efficacy of the method in high-throughput screening of LiBs cathode materials.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11304079,11404094,and 11504088)Science and Technology Research Project of Henan Science and Technology Department(Grant No.182102410076)。
文摘The capture of CO_(2)from CO_(2)/H_(2)gas mixtures in syngas is a crucial issue for hydrogen production from steam methane reforming in industry,as the presence of CO_(2)directly affects the purity of H_(2).A combination of a high-throughput screening method and grand canonical Monte Carlo simulation was utilized to evaluate and screen 1725 metal–organic frameworks(MOFs)in detail as a means of determining their adsorption performance for CO_(2)/H_(2)gas mixtures.The adsorption and separation performance of double-linker MOFs was comprehensively evaluated using eight evaluation indicators,namely,the largest cavity diameter,accessible surface area,pore occupied accessible volume,porosity,adsorption selectivity,working capacity,adsorbent performance score and percent regeneration.Six optimal performance frameworks were screened to further study their single-component adsorption and binary competitive adsorption of CO_(2)/H_(2)respectively.The CO_(2)adsorption selectivity at different CO_(2)/H_(2)feed ratios was also evaluated,which indicated their excellent adsorption and separation performance.The microscopic adsorption mechanisms for CO_(2)and H_(2)at the molecular level were investigated by analyzing the radial distribution function and density distribution.This study may provide directional guidance and reference for subsequent experiments on the adsorption and separation of CO_(2)/H_(2).
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2022R1F1A1074339)。
文摘For the advancement of fast-charging sodium-ion batteries(SIBs),the synthesis of cutting-edge cathode materials with superior structural stability and enhanced Na+diffusion kinetics is imperative.Multiphase layered transition metal oxides(LTMOs),which leverage the synergistic properties of two distinct monophasic LTMOs,have garnered significant attention;however,their efficacy under fast-charging conditions remains underexplored.In this study,we developed a high-throughput computational screening framework to identify optimal dopants that maximize the electrochemical performance of LTMOs.Specifically,we evaluated the efficacy of 32 dopants based on P2/O3-type Mn/Fe-based Na_(x)Mn_(0.5)Fe_(0.5)O_(2)(NMFO)cathode material.Multiphase LTMOs satisfying criteria for thermodynamic and structural stability,minimized phase transitions,and enhanced Na^(+)diffusion were systematically screened for their suitability in fast-charging applications.The analysis identified two dopants,Ti and Zr,which met all predefined screening criteria.Furthermore,we ranked and scored dopants based on their alignment with these criteria,establishing a comprehensive dopant performance database.These findings provide a robust foundation for experimental exploration and offer detailed guidelines for tailoring dopants to optimize fast-charging SIBs.
文摘Barrett's esophagus(BE) is a change in the esophageal lining and is known to be the major precursor lesion for most cases of esophageal adenocarcinoma(EAC).Despite an understanding of its association with BE for many years and the falling incidence rates of squamous cell carcinoma of the esophagus, the incidence for EAC continues to rise exponentially. In association with this rising incidence, if the delay in diagnosis of EAC occurs after the onset of symptoms,then the mortality at 5 years is greater than 80%. Appropriate diagnosis and surveillance strategies are therefore vital for BE. Multiple novel optical technologies and other advanced approaches are being utilized to assist in making screening and surveillance more cost effective. We review the current guidelines and evolving techniques that are currently being evaluated.
基金Supported by Partially funded by FESR P.O.Apulia Region 2007-2013-Action 1.2.4,No.3Q5AX31
文摘Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinicallyavailable diagnostic methods are mainly based on the use of either X-rays or ultrasound(US). All X-ray based methods provide a measure of bone mineral density(BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry(DXA) is considered the current 'gold standard' for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations(e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound(QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this 'silent disease' and show up recent advances for its prevention and improved management through early diagnosis.
基金the Science Challenge Project(TZ2018004)the National Natural Science Foundation of China(21875228 and 21702195)for financial support。
文摘Finding energetic materials with tailored properties is always a significant challenge due to low research efficiency in trial and error.Herein,a methodology combining domain knowledge,a machine learning algorithm,and experiments is presented for accelerating the discovery of novel energetic materials.A high-throughput virtual screening(HTVS)system integrating on-demand molecular generation and machine learning models covering the prediction of molecular properties and crystal packing mode scoring is established.With the proposed HTVS system,candidate molecules with promising properties and a desirable crystal packing mode are rapidly targeted from the generated molecular space containing 25112 molecules.Furthermore,a study of the crystal structure and properties shows that the good comprehensive performances of the target molecule are in agreement with the predicted results,thus verifying the effectiveness of the proposed methodology.This work demonstrates a new research paradigm for discovering novel energetic materials and can be extended to other organic materials without manifest obstacles.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82373835,82304437,and 82173781)Regional Joint Fund Project of Guangdong Basic and Applied Basic Research Fund,China(Grant Nos.:2023A1515110417 and 2023A1515140131)+2 种基金Regional Joint Fund-Key Project of Guangdong Basic and Applied Basic Research Fund,China(Grant No.:2020B1515120033)the Key Field Projects of General Universities in Guangdong Province,China(Grant Nos.:2020ZDZX2057 and 2022ZDZX2056)Medical Scientific Research Foundation of Guangdong Province of China(Grant No.:A2022061).
文摘Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.
文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.
基金supported by the Ministry of Science and Technology, PRC in Mega-projects of Science Research During the 10th Five-Year Plan Period (No. 2004AA2Z38784)National Natural Science Foundation of China (No. 30472026).
文摘Objective To develop a high-throughput screening assay for Farnesoid X receptor （FXR） agonists based on mammalian one-hybrid system （a chimera receptor gene system） for the purpose of identifying new lead compounds for dyslipidaemia drug from the chemical library. Methods cDNA encoding the human FXR ligand binding domain （LBD） was amplified by RT-PCR from a human liver total mRNA and fused to the DNA binding domain （DBD） of yeast GAL4 of pBIND to construct a GAL4-FXR （LBD） chimera expression plasmid. Five copies of the GAL4 DNA binding site were synthesized and inserted into upstream of the SV40 promoter of pGL3-promoter vector to construct a reporter plasmid pG5-SV40 Luc. The assay was developed by transient co-transfection with pG5-SV40 Luc reporter plasmid and pBIND-FXR-LBD （189-472） chimera expression plasmid. Results After optimization, CDCA, a FXR natural agonist, could induce expression of the luciferase gene in a dose-dependent manner, and had a signal/noise ratio of 10 and Z＇ factor value of 0.65, Conclusion A stable and sensitive cell-based high-throughput screening model can be used in high-throughput screening for FXR agonists from the synthetic and natural compound library.
基金supported by the State Key Laboratory of Natural and Biomimetic Drugs, Peking University。
文摘Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite their relevance in diseases and the variety of physiological functions they are involved in, ion channels still remain underexploited as drug targets. This, to a large extent, is attributed to the absence of screening technologies that ensure both the quality and the throughput of data. However, an increasing number of assays and technologies have evolved rapidly in the past decades. In this review, we summarized the currently available high-throughput screening technologies in ion channel drug discovery.
基金the South Carolina Smart State Center for Strategic Approaches to the Generation of Electricity (SAGE) for funding
文摘Efficient parallel screening of combinatorial libraries is one of the most challenging aspects of the high- throughput （HT） heterogeneous catalysis workflow. Today, a number of methods have been used in HT catalyst studies, including various optical, mass-spectrometry, and gas- chromatography techniques. Of these, rapid-scanning Fourier-transform infrared （FTIR） imaging is one of the fastest and most versatile screening techniques. Here, the new design of the 16-channel HT reactor is presented and test results for its accuracy and reproducibility are shown. The performance of the system was evaluated through the oxidation of CO over commercial Pd/AI203 and cobalt oxide nanoparticles synthesized with different reducer-reductant molar ratios, surfactant types, metal and surfactant concentrations, synthesis temperatures, and ramp rates.
基金supported by the Natural Science Foundation of China (Nos.21706106,21536001 and 21322603)the National Key Basic Research Program of China ("973") (No.2013CB733503)+1 种基金the Natural Science Foundation of Jiangsu Normal University(16XLR011)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The globally increasing concentrations of greenhouse gases in atmosphere after combustion of coal-or petroleum-based fuels give rise to tremendous interest in searching for porous materials to efficiently capture carbon dioxide(CO_2) and store methane(CH4), where the latter is a kind of clean energy source with abundant reserves and lower CO_2 emission. Hundreds of thousands of porous materials can be enrolled on the candidate list, but how to quickly identify the really promising ones, or even evolve materials(namely, rational design high-performing candidates) based on the large database of present porous materials? In this context, high-throughput computational techniques, which have emerged in the past few years as powerful tools, make the targets of fast evaluation of adsorbents and evolving materials for CO_2 capture and CH_4 storage feasible. This review provides an overview of the recent computational efforts on such related topics and discusses the further development in this field.
基金Project(31000350)supported by the National Natural Science Foundation of China
文摘Abstract： A simple optimized microplate-based method to assay endo-1,4-β-mannosidase activity was described as an improved high-throughput screening method. A series of experimental conditions were optimized. It is revealed that the optimum measurement procedure is as follows： adding 50μL of diluted enzyme sample and 50 μL substrate, incubating at 45 ℃ for exactly 5 min in micro-plate, mixing with 100 μL 3,5-dinitrosalicylic acid （DNS） reagent, maintaining at boiling point for 15 rain, cooling down to room temperature before determining the ABS value at 540 nm using an ELISA micro-plate reader. The reaction volume of the optimized microplate-assay is reduced to 200μL from 2 500 μL used in the standard β-mannanase macro-assay. The optimized micro-assay is significantly more sensitive in all of the 643 candidates during endo-1,4-β-mannosidase screening. Statistical analyses show that the sensitivity of the optimized micro-method is significantly greater than that of the macro-assay. The optimized method is convenient, fast, and cheap for high throughput enzyme screening.
基金Supported by the National Natural Science Foundation of China(Nos30400081, 30570405 and 20672045)the Key Tech-nology Research and Development Program of China(No2004BA713D03-04)
文摘To identify the desired hypertherrnophilic variants within a mutant esterase library for the resolution of （R, S）-2- octanol acetate, a simple, reliable, and versatile method was developed in this study. We built a screening strategy including two steps, first we selected agar plate with substrate to screen the enzymatic activity; secondly we used a pH indicator to screen the enantioselectivity. This method could rapidly detect favorable mutants with high activity and enantioselectivity. A total of 96. 2% of tedious screening work can be precluded using this screening strategy. It is an effective screening for alkyl ester and can be applied to relative screening researches. The four improved mutants were screened from the mutant esterase library. Their enantioselectivities, activities, and structures were investigated at different temperatures.
文摘To develop a new high-throughput screening model for human high-density lipoprotein （HDL） receptor （CD36 and LIMPⅡ analogous-1, CLA-1） agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA （cDNA） of CLA-1 was amplified by reverse transcription-polymerase chain reaction （RT-PCR）. Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus （AcNPV） into donor vector pFastBacl and recombinant pFastBacl-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacrnid DNA. Recombinant bacrnid-CLA-1 was transfected into Spodopterafrugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA- 1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.
基金the National Key R&D Program of China(Grant No.2018YFA0702100)the National Natural Science Foundation of China(Grant No.U21A2079)+2 种基金the Beijing Natural Sci-ence Foundation(Grant No.2182032)the Zhejiang Provincial Key R&D Program of China(Grant Nos.2021C01026 and 2021C05002)and the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2020R01007).
文摘Thermoelectric materials have drawn extensive interest due to the direct conversion between electricity and heat,however,it is usually a time-consuming process for applying traditional“sequential”meth-ods to grow materials and investigate their properties,especially for thermoelectric films that typically require fine microstructure control.High-throughput experimental approaches can effectively accelerate materials development,but the methods for high-throughput screening of the microstructures require further study.In this work,a combinatorial high-throughput optimization solution of material properties is proposed for the parallel screening and optimizing of composition and microstructure,which involves two distinctive types of high-throughput fabrication approaches for thin films,along with a new portable multiple discrete masks based high-throughput preparation platform.Thus,Bi_(2)Te_(3-x)Se_(x)thin film library with 196 throughputs for locating the optimized composition is obtained in one growth cycle.In addition,another thin film library composed of 31 materials with traceable process parameters is built to further investigate the relationship between microstructure,process,and thermoelectric performance.Through high-throughput screening,the Bi_(2)Te_(2.9)Se_(0.1)film with(00l)orientation is prepared with a peak zT value of 1.303 at 353 K along with a high average zT value of 1.047 in the interval from 313 to 523 K.This method can be also extended to the discovery of other functional thin films with a rapid combinatorial screening of the composition and structure to accelerate material optimization.
基金National Science and Technology Major Projects of Infectious Disease(grant number 2018ZX10731101)。
文摘Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul virus.No approved antiviral drugs are available for these hantaviral diseases.Here,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources.We identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases.Overall,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS therapy.These findings may offer a starting point for the treatment of patients infected with hantaviruses.
基金partially supported by the National Key R&D Program of China (grant 2018YFC1200602 and 2016YFD0500403 to RHH)。
文摘Zika virus(ZIKV) is associated with severe birth defects and Guillain-Barre′ syndrome and no approved vaccines or specific therapies to combat ZIKV infection are currently available. To accelerate anti-ZIKV therapeutics research, we developed a stable ZIKV GFP-reporter virus system with considerably improved GFP visibility and stability. In this system a BHK-21 cell line expressing DC-SIGNR was established to facilitate the proliferation of GFP-reporter ZIKV. Using this reporter virus system, we established a high-throughput screening assay and screened a selected plant-sourced compounds library for their ability to block ZIKV infection. More than 31 out of 974 tested compounds effectively decreased ZIKV reporter infection. Four selected compounds, homoharringtonine(HHT), bruceine D(BD), dihydroartemisinin(DHA) and digitonin(DGT), were further validated to inhibit wild-type ZIKV infection in cells of BHK-21 and human cell line A549.The FDA-approved chronic myeloid leukemia treatment drug HHT and BD were identified as broad-spectrum flavivirus inhibitors. DHA, another FDA-approved antimalarial drug effectively inhibited ZIKV infection in BHK-21 cells. HHT, BD and DHA inhibited ZIKV infection at a post-entry stage. Digitonin was found to have inhibitory activity in the early stage of viral infection. Our research provides an efficient high-throughput screening assay for ZIKV inhibitors. The active compounds identified in this study represent potential therapies for the treatment of ZIKV infection.
